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谷氨胺缺乏会增强TCA循环酶的核定位和表观遗传修饰,损害肌体发生

Angad Yadav¹, Susan Schmitt¹, Wenxia Ma¹

¹Department of Cell Developmental and Integrative Biology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States.

American journal of physiology. Cell physiology

|December 5, 2025

概括

细胞外谷氨酸 (Gln) 对于肌肉干细胞的功能和再生至关重要. Gln 缺乏症通过改变代谢和表观遗传状态来损害肌肉发育,影响肌肉生长至关重要的基因调节.

科学领域:

肌肉生物学肌肉生物学
细胞代谢的细胞代谢.
表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.

背景情况:

细胞外谷氨酸 (Gln) 对肌肉原生细胞 (MPC) 功能至关重要,特别是在衰老或代谢性压力期间.
Gln的可用性通过调节细胞内代谢和表观遗传状态来影响MPC的扩散.

研究的目的:

为了研究细胞外 Gln 如何调节 MPC 增殖和肌细胞生成.
阐明将Gln可用性与肌肉发育中的表观遗传修饰和基因调控联系起来的分子机制.

主要方法:

利用了人类的原发性肌细胞和小鼠的C2C12肌细胞细胞系.
在不同的Gln条件下评估细胞活力,细胞周期进展和MyoD表达.
分析了TCA循环酶的核定位,基因素糖化水平,以及在Myod1位点的染色质可访问性.

主要成果:

Gln缺乏减少了细胞活力,诱导了G0/G1细胞周期停止,并降低了MyoD表达的调节,抑制了肌肉生成.
Gln 缺乏增加了α-甲酸脱酶复合组件 (DLST,OGDH) 的核定位.
在 Gln 缺陷条件下,观察到基因酸的升高和Myod1位点的染色质可访问性降低.

结论:

细胞外 Gln 是通过代谢-表观遗传轴 MPC 增殖的一个关键调节器.
缺少GLN会通过改变染色质状态和肌性基因调节来损害肌体发生.
这些发现突出了Gln在控制肌体发生过程中通过代谢介质控制染色质状态的关键作用.

关键词:

在TCA循环的分段化.染色质可访问性染色质可访问性谷氨胺的代谢过程肌肉发育 (myogenesis) 是一个过程.葡萄糖化葡萄糖化

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